PURPOSE: To investigate the frequency and patterns of headache in a well-defined and homogeneous group of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) patients.METHODS: One hundred consecutive MTLE-HS patients under comprehensive presurgical evaluation were evaluated from May 2009 to April 2010. A standardized questionnaire was applied according to the criteria of the International Headache Society (IHS). Headache diagnosis was based on the second edition of the International Classification of Headache Disorders (ICHD-II).RESULTS: Ninety-two patients (92%) had at least one headache episode during the previous 12 months. Migraine occurred in 51.9% of patients and tension-type headache (TTH) in 39.1%. Patients with migraine presented higher frequency (p=0.002) and severity of episodes (p<0.001), as well as lateralized pain (p=0.001) than individuals with TTH. MTLE-HS patients with unilateral HS and predominantly unilateral headache (irrespective of the type), presented pain ipsilateral to the HS (OR 8.5; CI 95%=2.1-35.1; p=0.003).CONCLUSIONS: Headache is a frequent clinical symptom of lateralizing value, which may share common pathophysiology with epileptogenesis among MTLE-HS patients.